Canadian Medicine News - Part 161

Your face is full of attention, full of listening. How I remember that face!…. How you trusted your power of listening, your state of attention…. I know now that this is why you devoted yourself to medicine….

—Jacob Needleman

… well, interesting that you should ask, but, yes, there have been several such incidents that stand out for me. May I tell you one of them? The first happened a few years ago, when a patient taught me an important lesson. I met a middle-aged Native gentleman on one of my regular visits to a nearby native community. This patient had come in because of a chalazion. When we finished discussing that issue, I asked him whether he had any other concerns; he said there were none. The waiting room was quiet, and I knew no one else was waiting, so we chatted. After years of visiting the community, the man and his name were unfamiliar to me. “So where are you from, what brought you this way?”

The idea of andropause (“male menopause”) has received widespread attention in the popular and medical press in the last few years. As men age, total testosterone levels decline gradually and concentrations of free and bioavailable testosterone decline sharply with each decade beyond the 30s.

Aging men often begin to experience symptoms such as sexual dysfunction (loss of libido, erectile dysfunction), weakness, fatigue, lethargy, insomnia, mood disorders, flushes, and less motivation. They also tend to lose bone density as they age and might not realize it until they fracture a bone. Are the symptoms and loss of bone related to falling testosterone levels? If so, for carefully selected men, will treatment with testosterone improve bone mineral density and relieve symptoms?

This paper will explore the emerging evidence for a relationship between falling testosterone levels and an increase in symptoms in aging men (an association conveniently called andropause), will urge physicians to look for low-normal or frankly low testosterone levels, and will suggest that many aging men’s lives will improve with testosterone treatment.

Level I evidence shows that continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) are effective for preventing intubation and saving the lives of carefully selected patients with acute respiratory failure. This article attempts to review this evidence.

We began by searching the literature, using OVID, looking for all randomized studies of congestive heart failure and respiratory failure. Use of CPAP and BiPAP for sleep apnea or chronic respiratory failure will not be explored.

In 1991, Frank A. Lederle identified highdose oral vitamin B12 (cobalamin) treatment for pernicious anemia as “medicine’s best kept secret.” Lederle noted that only mg of cobalamin is required for daily metabolic functions. Because 2.0% of oral vitamin B12 is absorbed by small bowel mucosa independent of intrinsic factor or the terminal ileum, a daily 1000-mg dose of oral cobalamin provides more than enough vitamin to patients with pernicious anemia as well as patients whose B12 deficiency is caused by atrophic gastritis or decreased intake.

Clinical studies with extensive follow up have found that B12 levels in patients with pernicious anemia remain normal with high-dose oral therapy. A recently published randomized trial found that oral B12 supplementation was superior to parenteral therapy for correcting serum B12, methylmalonic acid, and homocysteine levels. published clinical studies have not found high-dose oral B12 to be unsuccessful in treating patients.

Little is known in North America, however, about the effectiveness of oral B12 therapy. Several review articles regarding treatment of B12 deficiency have acknowledged oral B12 therapy or have supported its use. Three clinical studies favouring high-dose oral B12 therapy have also been published. Regardless, oral therapy is seldom used in North America despite being widely accepted elsewhere. Informal discussion with family physicians, who treat nearly all B12 deficiency in Canada, revealed that few use high-dose oral instead of parenteral B12 for replacement therapy.
Oral B12 therapy is advantageous for patients because it avoids repeated physician visits and painful injections. It can also save money. None of the articles retrieved from a MEDLINE search between 1966 and 1999 using the MeSH heading “vitamin B12” and the text word “oral” explicitly compared the costs of parenteral and oral B12 supplementation. With this study, we sought to determine the costs and potential savings of switching all elderly Ontarians from parenteral B12 to high-dose oral therapy.

Dr van Walraven is an Assistant Professor of medicine at the University of Ottawa, Principal Investigator at the Loeb Health Research Institute, and a scientist at the Institute for Clinical Evaluative Sciences (ICES) in Ontario. Dr Austin is an Associate Scientist at ICES. Dr Naylor is a Professor of Medicine at the University of Toronto and is Adjunct Senior Scientist at ICES.

Major depression is a common and debilitating disorder that affects 10% to 15% of the population each year. Advances in understanding the psychopharmacology of depression has lead to the introduction of several new classes of antidepressant medication in the past decade. Despite these advances, however, patients’ overall response to any given pharmacologic approach continues to be unsatisfactory. Only 50% of patients recover fully from depression with antidepressant therapy; 35% to 40% recover partially and continue to have residual symptoms; and 10% to 15% do not improve at all despite adequate trials (diagnosis, selection of medication, treatment time, and compliance) of *antidepressant medication.

The clinical importance of these figures is underscored by the fact that incomplete recovery from a primary depressive episode is associated with serious personal, economic, and psychosocial morbidity. Complications include prolonged suffering of patient and family, higher risk of suicide, increased medical and psychiatric comorbidity, loss of productivity, loss of income, erosion of social support, social withdrawal, and increased levels of dependency. Refractory patients, therefore, represent a dilemma for primary care providers.

How is refractory defined? One proposed operational definition of refractory depression is a poor or unsatisfactory response to two adequate trials (optimal dosage and duration) of two different classes of antidepressant medication after ruling out possible medical or organic causes of the condition (Table 1).

Deep vein thrombosis is feared for its potentially fatal complication, pulmonary thromboembolism (PE), the leading cause of preventable mortality among patients in hospital. Deep vein thrombosis affects both healthy people and many patients in hospital. Incidence of DVT is unknown because it is hard to diagnose and because most DVT is silent.

Pathophysiology

Venous thrombosis is triggered by damage to vessels, stasis of blood flow, and increased coagulability, factors classically known as Virchow’s triad. One or more of these factors comes into play with advancing age, cancer, surgery, immobilization, fractures, the puerperium, paralysis, oral contraceptive and estrogen use, antiphospholipid syndrome, and inherited thrombophilia. Inherited thrombophilic conditions include deficiencies of antithrombin, protein C or protein S; factor V Leiden; hyperhomocysteinemia; and other rare conditions. About 40% to 60% of patients having a first episode of DVT have inherited thrombophilic abnormalities.

The veins involved in DVT are lower limb (~85%); pelvic (~10%); and upper limb, shoulder, and cephalic (~5%). Whether calf vein thrombi cause clinically important PE is a matter of debate. Calf vein thrombi become dangerous if they propagate proximally, which occurs in about 20% of cases. Superficial thrombophlebitis not related to varicose veins or obvious etiology (eg, an intravenous catheter) has about a 40% risk of associated DVT.

Diagnosis of cancer during pregnancy is one of the most extreme scenarios in medicine: the creation of a new life might coincide with the mother’s death. This situation can put immense stress on pregnant patients, their families, and medical staff. Cancer occurs only rarely during pregnancy; incidence is 0.07% to 0.1%. The current trend to defer pregnancy until later in life might lead to increased incidence of cancer during pregnancy. There is, however, very little information on the effect of pregnancy on cancer and the effects of cancer and its therapy on pregnancy outcome. Because chemotherapeutic agents in current use have substantially increased longevity and survival, it is important that physicians ensure optimal treatment for mothers without harming their fetuses.

Most chemotherapeutic agents have been shown to damage rapidly dividing cells, such as bone marrow, intestinal epithelium, and reproductive organs. Animal studies suggest that a fetus would be similarly affected by these agents because fetal tissues have a high growth rate. This damage could result in spontaneous abortions or malformations.

Chemotherapeutic drugs are potent teratogens. Currently, there is very little information on the effect of cancer chemotherapy on fetuses. The risk of malformations when chemotherapy is administered during the first trimester has been estimated at 10% for single-agent chemotherapy and at 25% for combination chemotherapy. Thus, chemotherapeutic agents should be avoided during the first trimester.